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Molecular Cancer

, 15:33

First Online: 10 May 2016Received: 18 February 2016Accepted: 03 May 2016DOI: 10.1186-s12943-016-0519-1

Cite this article as: Davis, H.W., Hussain, N. & Qi, X. Mol Cancer 2016 15: 33. doi:10.1186-s12943-016-0519-1

Abstract

Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C SapC which is embedded in dioleoylphosphatidylserine DOPS vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for treatment. In addition, there is important evidence suggesting that SapC-DOPS may also prove to be an effective novel cancer therapeutic reagent. Given that SapC-DOPS is easily labeled with lipophilic dyes, it has been combined with the far-red fluorescent dye, CellVue Maroon CVM, for tumor targeting studies. We also have used contrast agents incorporated in the SapC-DOPS nanovesicles for computed tomography and magnetic resonance imaging, and review that data here. Administered intravenously, the fluorescently labeled SapC-DOPS traversed the blood–brain tumor barrier enabling identification of brain tumors. SapC-DOPS-CVM also detected a variety of other mouse tumors in vivo, rendering them observable by optical imaging using IVIS and multi-angle rotational optical imaging. Dye is detected within 30 min and remains within tumor for at least 7 days, whereas non-tumor tissues were unstained some dye observed in the liver was transient, likely representing degradation products. Additionally, labeled SapC-DOPS ex vivo delineated tumors in human histological specimens. SapC-DOPS can also be labeled with contrast reagents for computed tomography or magnetic resonance imaging. In conclusion, labeled SapC-DOPS provides a convenient, specific, and nontoxic method for detecting tumors while concurrently offering a therapeutic benefit.

KeywordsPhosphatidylserine Cancer Tumor imaging Contrast agents Saposin C SapC-DOPS AbbreviationsCTcomputed tomography

CVMCellVue Maroon

FDGfluorodeoxyglucose

MAROImulti-angle rotational optical imaging

MRImagnetic resonance imaging

PETpositron emission tomography

PSphosphatidylserine

SapC-DOPSsaposin C-Dioleophosphatidylserine

USPIOultra-small super-paramagnetic iron oxide

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Autor: Harold W. Davis - Nida Hussain - Xiaoyang Qi

Fuente: https://link.springer.com/







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